OP0038 VITAMIN D AND MARINE n-3 FATTY ACID SUPPLEMENTATION FOR PREVENTION OF AUTOIMMUNE DISEASE IN THE VITAL RANDOMIZED CONTROLLED TRIAL: OUTCOMES OVER 7 YEARS
Authors: K. Costenbader, N. Cook, I. M. Lee, J. Hahn, J. Walter, V. Bubes, G. Kotler, N. Yang, S. Friedman, E. Alexander, J. Manson
Journal: Annals of the Rheumatic Diseases (2022)

Background Strong biologic rationale supports both vitamin D and marine omega-3 (n-3) fatty acids for prevention of autoimmune disease (AD). Within the randomized, double-blind, placebo-controlled VIT amin D and Omeg A -3 Tria L ( VITAL ), we tested the effects of these supplements on AD incidence. We previously reported results after 5.3 years of randomized follow-up showing overall protective effects for vitamin D on AD incidence (HR 0.78, 95% CI 0.61-0.99) and suggestive results for n-3 fatty acids (HR 0.85, 95%CI 0.67-1.08) 1 . Objectives We aimed to test effects of these supplements with two more years of post-intervention follow-up in VITAL. Methods VITAL enrolled and randomized men and women (age ≥50 and ≥55 years, respectively) in a 2-by-2 factorial design to vitamin D 3 (2000 IU/d) and/or n-3 fatty acids (1000 mg/d) or placebo and followed for median 5.3 years. Here, we followed participants for another 2 years of observation to assess for sustained effects. Incident AD diagnoses were reported by participants annually and confirmed by medical record review by expert physicians using existing classification criteria. The primary endpoint was total incident AD, including rheumatoid arthritis (RA), polymyalgia rheumatica (PMR), autoimmune thyroid disease (AITD), psoriasis, and all others. Pre-specified secondary endpoints included individual common AD; and probable AD. Cox models calcuated hazard ratios (HR) for incident ADs. Results Of 25,871 participants randomized, 71% self-reported non-Hispanic Whites, 20% Black, 9% other racial/ethnic groups, 51% women, mean age was 67.1 years. During 7.5 years median follow-up, confirmed AD was diagnosed in 156 participants in vitamin D arm vs 198 in vitamin D placebo arm, HR 0.79 (0.64-0.97). Incident AD was confirmed in 167 participants in n-3 fatty acid arm and 187 in n-3 fatty acid placebo arm, HR 0.89 (0.72-1.10). For vitamin D, HRs trended toward reduction for RA 0.67 (0.37- 1.21), PMR 0.69 (0.46-1.03) and psoriasis 0.57 (0.33-0.99). For n-3 fatty acids, HRs trended toward reduction for RA 0.55 (0.30-1.10) and AITD 0.61 (0.33-1.12). Vitamin D’s effect on AD incidence was stronger in those with body mass index (BMI) &lt; 25 (HR 0.65, 0.44-0.96) than ≥ 25 kg/m 2 (p interaction 0.01). Conclusion Supplementation for 5.3 years with 2000 IU/day vitamin D (compared to placebo), followed by 2 years of observational follow-up, significantly reduced overall incident AD by 21% in older adults. HRs for RA, PMR and psoriasis trended toward reduction with vitamin D, with stronger effect in those with normal BMI. Supplementation with 1000 mg/day n-3 fatty acids did not significantly reduce total AD. References [1]Hahn J et al , BMJ, 2022 Jan 26;376: e066452. Table 1. Hazard Ratios for Primary and Secondary Endpoints, by Randomized Assignment to Vitamin D/Placebo (Left), N-3 Fatty Acids/Placebo (Right) a Endpoint Vitamin D 3 (N=12,927 ) Placebo (N=12,944 ) Hazard Ratio (95% CI ) p N-3 Fatty Acids (N=12,933 ) Placebo (N=12,938 ) Hazard Ratio (95% CI ) p Primary: Confirmed AD 156 198 0.79 (0.64-0.97 ) 0.03 167 187 0.89 (0.72-1.10) 0.27 Secondary: Confirmed + probable AD 265 321 0.83 (0.70-0.97 ) 0.02 271 315 0.86 (0.73-1.01) 0.06 Excluding subjects with any pre-randomization AD Confirmed AD 127 162 0. 79 (0.62-0.99 ) 0.04 141 148 0.95 (0.75-1.20) 0.66 Confirmed + probable AD 211 270 0. 78 (0.65-0.94 ) 0.007 232 249 0.93 (0.78-1.11) 0.41 Excluding first 2 years follow-up Confirmed AD 86 130 0.66 (0.50-0.87 ) 0.003 104 112 0.92 (0.71-1.21) 0.56 Confirmed + probable AD 147 205 0.72 (0.58-0.89 ) 0.002 172 180 0.95 (0.77-1.17) 0.63 Individual AD b RA 18 27 0.67 (0.37-1.21) 0.18 16 29 0.55 (0.30-1.01) 0.06 PMR 39 57 0.69 (0.46-1.03) 0.07 46 50 0.92 (0.61-1.37) 0.67 AITD 27 18 1.50 (0.82-2.71) 0.19 17 28 0.61 (0.33-1.12) 0.11 Psoriasis 20 35 0.57 (0.33-0.99 ) 0.05 34 21 1.62 (0.94-2.79) 0.08 a Analyses from Cox regression models controlled for age, sex, race, and other (n-3 fatty acid or vitamin D) randomization group b Confirmed AD. Figure 1. Disclosure of Interests Karen Costenbader Consultant of: Astra Zeneca, Glaxo Smith Kline, Neutrolis, Grant/research support from: Merck, Exagen, Gilead, Nancy Cook: None declared, I-min Lee: None declared, Jill Hahn: None declared, Joseph Walter: None declared, Vadim Bubes: None declared, Gregory Kotler: None declared, Nicole Yang: None declared, Sonia Friedman: None declared, Erik Alexander: None declared, JoAnn Manson: None declared.